Individuals exposed to cocaine (COC) in utero during the "epidemic" that began in the late 1980s now are entering adolescence and young adulthood. What neurocognitive (NC) impediments to anticipate, if any, as these young people encounter increasing demands in the academic arena and workplace are unclear. The long-term objective of this grant is exploration of the effects of gestational COC exposure on NC outcome of adolescents and young adults. While animal studies overwhelmingly find evidence of changes in brain function, human studies have yielded inconsistent results. We propose to refine the study of effects of prenatal COC exposure in humans by incorporating concepts and methods from cognitive neuroscience, advances in neuroimaging, and neuroscience of stress. We will test three hypotheses: 1) prenatal COC exposure affects NC outcome in adolescents and young adults;2) prenatal COC exposure produces effects on neural development identifiable by neuroimaging;and 3) prenatal COC exposure alters the regulation of stress response. In a 5-year prospective study of 120 low income urban African American adolescents followed since birth (1989-92), half with prenatal COC exposure and half without, for whom there is an extensive database (to include prior NC and neuroimaging data), we will: 1) semi-annually assess risk-taking (to include urine drug screens) and collect demographics;2) twice (once early, once late) assess NC function with a neurocognitive battery, and assess neural development through neuroimaging studies;and 3) on one occasion evaluate subjects'reponses to stressful stimuli using endocrine, autonomic, and behavioral measures. Statistical analyses will employ multivariate and longitudinal statistical models (mixed effect models, GEE, and latent trajectories models). As the cohort investigated here is one of the oldest being followed longitudinally, and for whom there are baseline NC and neuroimaging data, we have an almost unprecedented opportunity, through application of cognitive neuroscience, state of the art neuroimaging, and neuroscience of stress, to detect effects of prenatal COC exposure in adolescents and young adults. Results will inform regarding anticipated obstacles, if any, to the success of exposed youth in the next phases of their life trajectory - the academic arena and work place. Understanding long-term effects allows design of strategies to enhance youths'productivity and prepare them for responsibilities of adulthood.